Ferruti Paolo, Bianchi Sabrina, Ranucci Elisabetta, Chiellini Federica, Caruso Vincenzina
Dipartimento di Chimica Organica e Industriale, Università di Milano, via Venezian 21, 20133 Milano, Italy.
Macromol Biosci. 2005 Jul 14;5(7):613-22. doi: 10.1002/mabi.200500020.
Biodegradable and biocompatible amphoteric poly(amido-amine) (PAA)-based hydrogels, containing carboxyl groups along with amino groups in their repeating unit, were considered as scaffolds for tissue engineering applications. These hydrogels were obtained by co-polymerising 2,2-bisacrylamidoacetic acid with 2-methylpiperazine with or without the addition of different mono-acrylamides as modifiers, and in the presence of primary bis-amines as crosslinking agents. Hybrid PAA/albumin hydrogels were also prepared. The polymerisation reaction was a Michael-type polyaddition carried out in aqueous media. The PAA hydrogels were soft and swellable materials. Cytotoxicity tests were carried out by the direct contact method with fibroblast cell lines on the hydrogels both in their native state (that is, as free bases) and as salts with acids of different strength, namely hydrochloric, sulfuric, acetic and lactic acid. This was done in order to ascertain whether counterion-specific differences in cytotoxicity existed. It was found that all the amphoteric PAA hydrogels considered were cytobiocompatible both as free bases and salts. Selected hydrogels samples underwent degradation tests under controlled conditions simulating biological environments, i.e. Dulbecco medium at pH 7.4 and 37 degrees C. All samples degraded completely and dissolved within 10 d, with the exception of hybrid PAA/albumin hydrogels that did not dissolve even after eight months. The degradation products of all samples turned to be non-cytotoxic. All these results led us to conclude that PAA-based hydrogels have a definite potential as degradable matrices for biomedical applications.
基于两性聚(酰胺 - 胺)(PAA)的可生物降解且生物相容的水凝胶,其重复单元中含有羧基和氨基,被视为组织工程应用的支架。这些水凝胶是通过将2,2 - 双丙烯酰胺基乙酸与2 - 甲基哌嗪共聚,添加或不添加不同的单丙烯酰胺作为改性剂,并在伯二胺作为交联剂的存在下制备而成。还制备了杂化PAA/白蛋白水凝胶。聚合反应是在水性介质中进行的迈克尔型加成聚合反应。PAA水凝胶是柔软且可溶胀的材料。通过直接接触法,在水凝胶处于天然状态(即作为游离碱)以及与不同强度的酸(即盐酸、硫酸、乙酸和乳酸)形成盐的状态下,对成纤维细胞系进行细胞毒性测试。这样做是为了确定细胞毒性中是否存在抗衡离子特异性差异。结果发现,所有考虑的两性PAA水凝胶作为游离碱和盐时均具有细胞生物相容性。选定的水凝胶样品在模拟生物环境的受控条件下进行降解测试,即在pH 7.4和37℃的杜尔贝科培养基中。除了杂化PAA/白蛋白水凝胶即使在八个月后仍未溶解外,所有样品在10天内完全降解并溶解。所有样品的降解产物均无细胞毒性。所有这些结果使我们得出结论,基于PAA的水凝胶作为生物医学应用的可降解基质具有一定的潜力。